The research supported by this grant will continue our longterm commitment to understanding the prenatal development of the primate visual system and the genetic and epigenetic determinants of neuronal phenotype and connectivity. Our basic strategy remains to view the entire developing visual system in the rhesus monkey as an interacting unit. In this cycle we are emphasizing the specification of primate-specific color channels at the level of the retina (e.g., red-green, blue cones), the development of parallel color-opponent or parvocellular (P) and broad-band or magnocellular (m) thalamic pathways that are thought to underlay color and form/motion perception, and the incorporation of these channels into cortical maps. Experiments on the retina will focus on determinants of the photoreceptor mosaic and cell phenotypes as well as the establishment of separate channels of retinofugal connections. Studies on the lateral geniculate will examine the specification of the thalamic relay neurons that form the M and P system and may coordinate development of both retinal and cortical maps. In cerebral cortex we pursue the areal, modular, laminar and local synaptic specification of areas 17, 18 and MT and their color and noncolor processing channels. The issues addressed will require a battery of methods including: retroviral gene transfer technique to determine lineage relationship among cells in the retina and LGN, immunocyto- and histochemistry ( e.g. antibodies to red/green- and blue-sensitive cones to expose the emergence of photoreceptor phenotypes, or CAT-301 to display motion related components in the cortex), application of In vitro autoradiography and in situ hybridization to reveal the emergence and distribution of major neurotransmitter receptors, analysis of neuronal connectivity using axonal markers (e.g. HRP, fluorescent or carbocianin dyes) and confocal and electron microscopy to study the development of cell dendritic pattern and synaptic connectivity. The studies will be carried out over a five year period in a series of normal and experimentally perturbed developing macaque monkeys. The experiments are designed in a way that tissue from each animal is used for multiple purposes, providing correlative developmental data and maximizing the amount of information from scarce and valuable primates. The underlying strategy is to discern how developmental events are orchestrated between the periphery and brain centers and to elucidate their involvement in congenital and acquired defects of vision.